How similar are protein folding and protein binding nuclei? Examination of vibrational motions of energy hot spots and conserved residues

Abstract

The underlying physico-chemical principles of the interactions between domains in protein folding are similar to those between protein molecules in binding. Here we show that conserved residues and experimental hot spots at intermolecular binding interfaces overlap residues that vibrate with high frequencies. Similarly, conserved residues and hot spots are found in protein cores and are also observed to vibrate with high frequencies. In both cases, these residues contribute significantly to the stability. Hence, these observations validate the proposition that binding and folding are similar processes. In both packing plays a critical role, rationalizing the residue conservation and the experimental alanine scanning hot spots. We further show that high-frequency vibrating residues distinguish between protein binding sites and the remainder of the protein surface.